Treatment for cerebral palsy impaired speech in children

ABSTRACT

Cerebral palsy impaired speech in children and adolescents are effectively treated by administration of a psychostimulant. Low doses of the psychostimulant significantly (p=0.0025) increases the percentage of correctly pronounced intelligible syllables or words and the ability to more intelligibly communicate (p=0.0309). The improvement in speech persists after cessation of or prior to continued psychostimulant treatment.

PRIOR RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 14/059,541, filed Oct. 22, 2013, and claims priority to U.S.patent application Ser. No. 14/059,541, filed Oct. 22, 2013 which is acontinuation-in-part of U.S. patent application Ser. No. 14/112,065,filed Oct. 16, 2013, and claims priority to U.S. Ser. No. 14/112,065,filed Oct. 16, 2013 and PCT/US2012/038312, filed May 17, 2012, and toprovisional application No. 61/487,847, filed May 19, 2011, whichapplications are incorporated herein in their entireties by referencethereto.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to cerebral palsy impaired speech. This inventionalso relates to evaluating a subject for and the treatment of speechimpairment secondary to cerebral palsy. In one specific aspect, thisinvention relates to the treatment of cerebral palsy impaired speech inchildren and adolescents. This invention also relates to speech,language and communication disorders in children diagnosed with cerebralpalsy.

2. Background and Discussion of the Art

Cerebral palsy (CP) is a non-progressive disease or disorder involvingirreparably damaged or injured areas of the brain, including connectionsbetween the cortex and other parts of the brain (the central nervoussystem) and the muscles (in the peripheral nervous system).

The National Institute of Neurological Disorders and Stroke (NINDS) ofthe National Institutes of Health (NIH) defines cerebral palsy as any ofa number of neurological disorders that appear in infancy or earlychildhood and permanently affect body movement and muscle coordinationbut do not worsen over time, and then makes clear that cerebral palsycannot be cured, but treatment will often improve a child's capabilitiesand that such treatment may include physical and occupational therapy,speech therapy, medications to control seizures, relax muscle spasms,and alleviate pain; surgery to correct anatomical abnormalities orrelease tight muscles; braces and other orthotic devices; wheelchairsand rolling walkers; and communication aids such as computers withattached voice synthesizers.

There are several causes of cerebral palsy, including maternal trauma orinfection resulting in periventricular leukomalacia, genetic mutationsresulting in cerebral dysgenesis; fetal stroke resulting intracranialhemorrhage, and hypoxic-ischemic encephalopathy. The several causes ofcerebral palsy include complications before birth. Such complicationsmay include genetic mutations, resulting in cerebral dysgenesis,maternal or fetal infections, resulting in encephalomalacia andintra-utero vascular thrombosis (intrauterine strokes). Complicationsduring delivery may result in hypoxic-ischemic encephalopathy. Afterbirth, CP can be the result of non-accidental trauma, encephalitis ormeningitis due to any number of infectious or toxic agents.

There are generally three types of cerebral palsy namely (1) ataxicwhich includes lack of muscle coordination, (2) spastic, which includestighter muscles and exaggerated reflexes and movements, and (3)dyskinetic movements, which includes slow and uncontrollable withering.Spastic cerebral palsy is further defined as spastic diplegia andspastic quadriplegia.

Dysarthria is one of many speech disorders seen in children withcerebral palsy, resulting from the inability of the central nervoussystem to coordinate and synchronize the muscles required for theproduction of speech. This encompasses the laryngeal, vela-pharyngeal,and oral musculature in coordination with the muscles responsible forrespiration that must work together in order to produce intelligiblespeech. Dysarthria can be classified as mild to moderate, wherein thepatient slurs at least some words and, at best, can be understood withsome difficulty; or severe, wherein the patient's speech is so slurredas to be unintelligible. Cerebral palsy is a cause of dysarthria. One ofthe speech impairments secondary to cerebral palsy is dyarthric speech.The inability to make articulatory contacts in order to produce bilabialsounds is considered a severe form of dysarthria. Dysarthria is one ofthe speech impairments treated by the present invention.

The National Institutes of Health (NIH) summary on the status of speechtherapy, to improve the speech of children with cerebral palsy statesthat treatment is currently limited to the enhancement of naturalcommunication forms such as communication symbols and charts or devicesthat generate synthetic speech and in training communications partners.

Intensive speech and language therapy over the course of several weeks,such as disclosed in Intensive Speech and Language Therapy for OlderChildren with Cerebral Palsy; a Systems Approach, Pennington et al.,Developmental Medicine & Child Neurology; 2010, 52: 337-344, reports atbest a 1.14 fold increase to 1.16 fold increase in the number of singleor multiple word responses.

Various mechanical and electro-mechanical devices including electrodesare disclosed in the prior art for treating cerebral palsy impairedspeech in children. Such devices are disclosed in U.S. Pat. No.5,213,553, issued May 25, 1993 to Light; and US2006f0161218, publishedJul. 20, 2006 to Danilov. Such treatments have had limited improvementin cerebral palsy impaired speech.

The art related to treating a speech impairment secondary to cerebralpalsy in children desires a treatment that readily and substantiallyimproves the impairment. The art also desires a treatment as aforesaidwherein the improvement in speech persists without the need forcontinuous treatment. The present invention accordingly provides asolution.

SUMMARY OF THE INVENTION

This invention, in one principal aspect, is the psychostimulanttreatment of a speech and language impairment secondary to cerebralpalsy. The invention in another aspect is the psychostimulant treatmentof dysarthria in children and adolescents.

This invention in another principal aspect is the evaluation of asubject for the psychostimulant treatment of a speech impairmentsecondary to cerebral palsy. More specifically, the invention is amethod for evaluating a subject for the psychostimulant treatment of aspeech impairment secondary to cerebral palsy by diagnosing the subjectas having cerebral palsy, determining that the subject has a resultantspeech impairment, and then determining that the subject has thresholdcognitive capability, and wherein when the subject has cerebral palsyimpaired speech and the threshold cognitive capability, the subject is acandidate for psychostimulant treatment to improve the impaired speech.The criteria used to select participants for this invention includes amedical and developmental history and pediatric neurologicalexamination, in addition to a diagnosis of cerebral palsy. Theclassification of the patient's specific cerebral palsy (e.g. spastic,ataxic, and or dyskinetic) was not particularly a parameter that wasconsidered. The candidates for treatment were required to posses thecognitive abilities equivalent to that of a two year old child. Theseskills included but were not limited to following two-stage unrelatedcommands, using a fisted grasp on a pencil to produce vertical strokeson paper and in the non-verbal child, the ability to sequence hislimited vocalizations and body movements to a rhythm when modeled (e.g.,beat gestures develop at 24-27 months). In addition the participants MRIscans (when available) are assessed to determine (a) a damaged portion,(b) a substantially intact frontal lobe and (c) an undamaged portionextending from the substantially intact frontal lobe to the auditorycortex.

This invention in a more specific aspect is a method for treatingcerebral palsy impaired speech in children and adolescents by theadministration of a therapeutically effective dose of a psychostimulantto effect a decrease in the difference between chronological age andspeech-language equivalent age. In one specific aspect, the presenttreatment results in the ability to accurately achieve articulatorycontacts to produce sounds, and enables the patient to begin producingsyllables and words.

The invention is, in one further aspect, a dosage regimen for thetreatment of cerebral palsy severe dysarthria by administration of amodest dose of a psychostimulant, with immediate resultant improvementof the impaired speech. The periodic administrations of thepsychostimulant over the course of several weeks and/or months, resultsin a 20-50% improvement the patients ability to produce sounds,syllables and/or words.

Without wishing to be bound by any theory or mechanism, it is believedthat the administration of a psychostimulant in a child or adolescentwith a speech impairment secondary to cerebral palsy creates alternateneural pathways between the central nervous system and those muscles inthe peripheral nervous system responsible for speech production, whichneural pathways circumvent the inoperable or damaged portions of thebrain.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the speech-language age equivalence of Participant 1 beforeand after treatment pursuant to the present invention;

FIG. 2 shows the percent of correct speech imitations for Participant 1over the course of the treatment sessions;

FIG. 3 shows the percent of correct responses by Participant 1 insession 6;

FIG. 4 shows the improvement in speech-language age equivalence forParticipant 2;

FIG. 5 shows the percent of correct speech imitations by Participant 2;

FIG. 6 shows the improvement in speech-language age equivalence forParticipant 3;

FIG. 7 shows the percent correct responses for Participant 3;

FIG. 8 shows the improvement in speech-language age for Participant 4;

FIG. 9 shows the percent of correct speech responses for Participant 4;

FIG. 10 shows the improvement in speech-language age equivalence forParticipant 5;

FIG. 11 shows the percent of correct speech imitations for Participant5;

FIG. 12 shows the percent of correct speech responses for Participant 6for Sessions 1;

FIG. 13 shows the percent of correct speech responses for Participant 6for Session 2; and

FIG. 14 shows a summary and comparison of the percent correct speechresponses for all the Participants, before and after the treatmentsessions.

BACKGROUND OF THE INVENTION Definitions

The term “subject” as used hereinbefore and hereinafter means a human orother mammal, and includes a patient or participant in a study orclinical trial.

The term “therapeutically effective dose” or “therapeutically effectivedosage” as used hereinbefore and hereinafter means an amount of theadministered substance that is sufficient to provide an improvement ofthe speech impairment.

The term “psychostimulant” as used hereinbefore and hereinafter isbroadly defined as a drug having antidepressant or mood-elevatingproperties, and as further discussed hereinafter.

The term “speech impairment secondary to cerebral palsy” is an artcognizable term and further contemplates language impairments.

The term “bilabial consonants” as used hereinbefore and hereinaftermeans, in the English language, the consonants m/p/b/w and “non-bilabialspeech” means the inability to correctly pronounce one of more of thebilabial consonants.

The term “speech-language age equivalence” or “speech-languageequivalent age” is the functional speech age of the participant, asdetermined by a speech language pathologist by methodologies well-knownin the speech therapy art.

EXAMPLES

In each of the following examples, the number of correctly pronouncedintelligible syllables or words, if any, prior to administration of thepsychostimulant is measured against the correctly pronouncedintelligible syllables or words after administration of thepsychostimulant. Specifically, correctly produced sounds, syllables orwords and the use of language prior to the administration of thepsychostimulant is used as a baseline to measure against a participant'sproduction after the administration of psychostimulant.

Participant 1

Participant 1 is a 16 year old boy diagnosed with non ambulatory spasticquadriplegic cerebral palsy resulting from hypoxic-ischemicencephalopathy (i.e., lack of oxygen to the brain during birth. An MRIwas not available for evaluation. Before the first treatment session(Session 1), Participant 1 could not imitate sounds, was unable toproduce modeled sounds in isolation or at the beginning, middle or endof words, was unable to pronounce his own name and had no cognizablesound production. Participant 1, before treatment, had a speech-languageage equivalence of a 3 month old child. Age equivalency was determinedusing the guidelines for vowel and final consonant acquisition. (McLeodS. Child Speech Acquisition). The speech-language age equivalency wasmeasured before the administration and approximately 30 minutes afterthe administration of the psychostimulant methylphenidate in periodictreatment sessions. Participant 1 was administered methylphenidate 5.0mg/day approximately three times a week and was evaluated during 6sessions over a 6 month period (approximately at 1 month intervals).Participant 1 was provided with the art cognizable PROMPT assistancetechniques administered by a speech therapist before and afteradministration of the psychostimulant methylphenidate in treatmentSessions 1-5. The number of correct or intelligible response wasmeasured before and after each treatment session. Participant 1 has acognitive functional age of a 3½ year old child, as determined bynon-verbal techniques well known in the field.

Participant 1, prior to the first administration of methylphenidate inSession 1 correctly imitated 5 words in 52 attempts. After the firstadministration of the medication, Participant 1 correctly imitated 18words in 56 attempts. Participant 1, as reported in Table I below,correctly imitated 9.61% of the speech before the initial administrationof 5.0 mg methylphenidate, and within about 30 minutes after the initialadministration correctly imitated 32.14% of the speech, or an about 3.35fold improvement in the percentage of correct speech imitations.

FIG. 1 shows the speech-language age equivalence vs. the actual age forParticipant 1 over the course of treatment. After six months,Participant 1 had established a speech-language equivalent age of about25 months. Participant 1 had a phonetic improvement that persisted afterthe methylphenidate was no longer efficaciously present in the subjectand prior to a subsequent administration of methylphenidate.

FIG. 2 shows bar graphs representing the percent of correct wordimitations over the course of five treatment sessions. The verticallines in all bar graphs represent the range of measurements for each setof evaluations. The (Before) bar graphs and averaging slope line forSessions 1-5 demonstrate a continued persistent improvement.

FIG. 3 shows the percent of correct responses before and after treatmentfor Participant 1 in Session 6. Session 6 is particularly significant inthat Participant 1 was for the first time challenged with polysyllabicwords. Participant 1 was afforded no PROMPT assistance before or afteradministration of the psychostimulant methylphenidate in thepolysyllabic word challenge of Session 6. In Session 6, Participant 1correctly imitated 31.87% of the polysyllabic words prior toadministration of the methylphenidate and 50% of the polysyllabic wordsafter administration of the methylphenidate, or an about a 1.57 foldimprovement (FIG. 3).

Table I shows the percent of correct speech imitations for Participant 1and the percent improvement for each session.

TABLE I Percent of Correct Speech Imitations for Participant 1 TREATMENTSESSIONS BEFORE AFTER DIFFERENTIAL Session 1  9.61% 32.14% 22.53 Session2 26.83% 33.96% 7.13 Session 3 30.68% 43.81% 13.13 Session 4 34.62% 61.9% 27.28 Session 5 38.98% 57.14% 18.16 Session 6 31.87% 50.00% 18.13

Participant 2

Participant 2 is a 13 year old girl from a Spanish speaking environment.Participant 2 was diagnosed with spastic hemiplegic cerebral palsyresulting from hypoxic ischemia encephalopathy cerebral palsy.Participant 2 presented with unintelligible speech, consisting ofinaudible vowel sounds. An MRI for Participant 2 showed symmetric areasof gliosis and encephalomalacia involving bilateral temporal, frontaland parietal lobes consistent with chronic infarcts in the vascularterritories of the middle cerebral arteries. There were smaller focalareas of encephalomalacia and gliosis involving the occipital lobes,right greater than the left. It was determined that Participant 2 had acognitive capability age of at least about a 2 year old. Prior totreatment, Participant 2 had a speech-language age equivalence of a 3month old, determined by using guidelines for vowel and consonantacquisition (McLeod S. Children's Speech Acuisition). Participant 2 wastreated with 5.0 mg of methylphenidate in three treatment sessions overa period of approximately three months. The participant utilized themedication approximately three times per week to practice with familymembers. The speech-language age equivalence was measured before andapproximately 30 minutes after each administration in the treatmentsession.

FIG. 4 shows the improvement in speech-language age equivalence forParticipant 2 from the date of first treatment wherein prior to thefirst treatment Participant 2 had a speech-language age equivalence of athree month old, and after three treatment sessions over a three monthperiod, Participant 2 had a speech-language equivalence of a 14 monthold.

FIG. 5 shows the percent of correct imitations of speech for threesuccessive treatment sessions. The FIG. 5 linear slope (Before)demonstrates the persistent increasing percentage of correct speechimitations, even before subsequent administrations of themethylphenidate in the treatment session. The vertical lines in all bargraphs represent the range of measurements before and afteradministration of the psychostimulant.

Referring specifically to FIG. 5 the percentage of correctly pronouncedsyllables or words was about 10% prior to a first administration of thepsychostimulant methylphenidate and more than 30% after a singleadministration of the psychostimulant methylphenidate, or an increase ofabout 3.4 fold increase. In Session 1, Participant 2 initially could notpronounce most of the sounds and syllables prior to the administration,but the percentage of correctly pronounced sounds and syllables modeledafter Session 2 administration was more than 50%. The percentage ofcorrectly pronounced and intelligible syllables or words, both beforeand after administration of the psychostimulant methylphenidategenerally progressively increased from session 1 through session 3. Thisdemonstrates persistent continued improvement, in contradistinction totransient improvement, in the improvement of the speech impairment.There was persistent improvement, even when the psychostimulant was nolonger efficaciously present in the body.

Table II shows the percent of correct speech imitations for Participant2.

TABLE II Percent of Correct Speech Imitations for Participant 2 SESSIONSBEFORE AFTER DIFFERENTIAL Session 1   10% 34.09% 24.09 Session 2 21.21%28.57% 7.36 Session 3 50.63% 55.77% 5.14

Participant 3

Participant 3 is an 8 year old girl with a Spanish speaking environmentin early childhood. Participant 3 was diagnosed with spastic diplegiccerebral palsy due to periventricular leukomalacia resulting from an inutero stroke. An MRI was not available for evaluation. Participant 3,prior to treatment pursuant to the present invention, had the capacityto vocalize one word or at best a two word phrases using presentprogressive when provided with a visual or pictorial prompt, and had aspeech-language equivalent age of a two year old. Participant 3's ageequivalence was determined by assessing mean length of utterance andchanges in grammatical structure (reference for first years, LS guide tocommunication milestones). Participant 3 was administered a dose of 5.0mg/twice per day of methylphenidate, once after breakfast and once afterschool. Participant 3 was evaluated 2 times at a 6 month interval. Aftersix months, Participant 3 could speak four and five word phrases whenprovided with a visual or pictorial prompt.

FIG. 6 shows the improvement in speech-language equivalence forParticipant 3 over the course of two treatment sessions.

FIG. 7 shows the percent correct multi-word responses for Participant 3after two treatment sessions. It is important to note that Participant 3was challenged with more difficult phrases in the second session than inthe first session and yet demonstrated improvement. Table III shows thepercent of correct speech imitations for Participant 3.

TABLE III Percent of Correct Speech Imitations for Participant 3SESSIONS BEFORE AFTER DIFFERENTIAL Session 1 66.67%  100% 33.33 Session2 77.55% 81.82% 4.27

Participant 4

Participant 4 is an 8 year old girl with an Arabic speaking environmentin early childhood. Participant 4 was diagnosed with spastic hemiplegiccerebral palsy resulting from a vascular accident and Protein Cdeficiency. The MRI for Participant 4 showed a large area ofencephalomalacia in the right temporal and posterior frontal lobe withWallerian degeneration and atrophy involving the right thalamus andright brain stem from the midbrain down to the medulla on the rightside. Participant 4, prior to treatment, produced on average two wordphrases and predominantly made use of present progressives having aspeech-language equivalent age of 24 months. Participant 4's languageability was assessed by determining changes in language ability andaverage phrase length. Participant 4 was administered 5.0 mg/day ofmethylphenidate in three treatment sessions spread over the course of 2months. By the end of 2 months (3 sessions) Participant 4 averageresponse phrase length increased to five words, reflecting aspeech-language age equivalence of a 6 year old (72 mos.).

FIG. 8 shows the improvement in speech-language equivalent age forParticipant 4.

FIG. 9 shows the percent of correct speech responses for Participant 4.As demonstrated by the linear (Before) averaging slope, there is apersistent increase in the percent of correct responses, even prior tothe administration of the psychostimulant in a subsequent treatmentsession. Table IV shows the percent of correct speech imitations forParticipant 4.

TABLE IV Percent of Correct Speech Imitations for Participant 4 SESSIONSBEFORE AFTER DIFFERENTIAL Session 1 63.33%  76% 12.67 Session 2 76.47%87.5% 11.03 Session 3 78.95% 88.14%  9.19

Participant 5

Participant 5 is a five year old girl with a Spanish speakingbackground. Participant 5 was diagnosed with genetic mutation cerebralpalsy resulting in speech impairment. An MRI was not available forevaluation. Participant 5, prior to treatment, had unintelligible speechof about one or two word phrases, accompanied by multiple errors inarticulation. Participant 5 had a cognitive ability greater than that ofa two year old and language-eqivalency age of 24 months, determined byacquisition of consonant and vowel sounds and mean length of utterances.Prior to treatment, participant 5 was unable to imitate phonemesappropriate for a three-year old. After treatment with 5.0 mgmethylphenidate in four monthly treatment sessions, Participant 5 wasable to intelligently pronounce some consonants and polysyllabic wordsand phrases.

FIG. 10 shows the improvement in speech-language equivalence age forParticipant 5 over the four monthly treatment sessions. FIG. 11 showsthe percent correct speech imitation for Participant 5 over the courseof the four treatment sessions. The linear (Before) averaging slope linedemonstrates the persistent improvement in the percent of correct speechimitations over the course of treatment sessions, and continuedimprovement before psychostimulant administration in a subsequenttreatment session.

Table V shows the percent correct speech imitations for Participant 5before and after administration of the methylphenidate over the courseof the four treatment sessions.

TABLE V Percent of Correct Speech Imitations for Participant 5 TREATMENTSESSIONS BEFORE AFTER DIFFERENTIAL Session 1 23.68% 47.62% 23.94 Session2 23.53% 54.05% 30.53 Session 3 43.75% 48.98% 5.23 Session 4 42.34%59.18% 16.81

Participant 6

Participant 6 is a 16 year old adolescent boy. Participant 6 wasdiagnosed with Trisomy21 (Down Syndrome) cerebral palsy resulting inspeech impairment. An MRI was not available for evaluation. On initialassessment, his speech was stuttered and unintelligible. Participant 6had the speech-language equivalent age of a 24 month old as determinedby types of sounds produced.

In Session 1, after baseline evaluation, a 5.0 mg dose ofmethylphenidate was administered. Upon re-evaluation, no improvement wasnoted.FIG. 12 shows the percent of correct responses for Session 1. A 10 mgdose of the amphetamine Dextroamphetamine was administered in Session 2.Between Sessions 1 and 2, there was a 10 day period in which Participant6 received 5.0 mg methylphenidate/day. During this 10 day periodParticipant 6 experienced adverse side effects including loss ofappetite and difficulty sleeping. Dextroamphetamine was accordinglyadministered in Session 2. In Session 2, there was an increase in thespeech-language equivalent to a 36 month old. FIG. 13 shows the percentof correct responses by Participant 6 in session 2.

Table VI shows the numerical percent correct responses in Sessions 1 and2. Table VI demonstrates that in Session 2, Participant 6 showed anabout 17% increase in the percent correct responses after the singleadministration of 10 mg of dextroamphetamine. Participant 6 had anapparent substantial increase in vocabulary access.

It is known in the art that certain non-verbal adolescents haveself-promoting gestures to compensate for inadequate vocabulary. Suchgestures were measured in Participant 6 before and after Sessions 1 and2. There was a substantial decline in such gestures after Session 2.This decline experientially correlates with an increased access to anduse of vocabulary.

TABLE VI Percent of Correct Responses for Participant 6 TREATMENTSESSIONS BEFORE AFTER DIFFERENTIAL Session 1 63.16% 59.26% −4.10 Session2 69.05% 85.71% 16.66

Summary of Results for all 6 Participants

FIG. 14 shows the percent of correct speech responses for all theParticipants prior to the first treatment session and after the finaltreatment sessions as discussed hereinbefore. FIG. 14 demonstrates thatthere are increases in the percent of correct speech responses fordiverse speech impairments secondary to different types of cerebralpalsy in 6 different children and adolescents, Table VII shows thepercent of correct speech responses for all Participants.

TABLE VII Percent of Correct Responses for All Participants NUMBERINITIAL FINAL PARTIC- OF PRESEN- ASSESS- DIFFER- IPANT AGE SESSIONSTATION MENT ENTIAL Participant 1 16 6  9.61% 50.00% 40.39 Participant 213 3   10% 28.57% 18.57 Participant 3 8 2 66.67% 81.82% 15.15Participant 4 8 3 63.33% 88.14% 24.81 Participant 5 5 4 23.68% 59.18%35.50 Participant 6 15 2 63.16% 85.71% 22.55

Anecdotal evidence, particularly by the parents or guardians of theParticipants, demonstrates that the speech and language improvements, inturn, effected improvements in and retention of socialization skills andemotional well being. The literature suggests that improvements inspeech and language functionality correlate with an increase in survivalskills and longevity (Katz, R., Life Expectancy for Children withCerebral Palsy and Mental Retardation: Implications for Life CarePlanning).

A repeated T-test was utilized as a statistical analysis of thedifference in speech-language ability before and after treatment; a Pvalue of <0.05 was considered significant and with respect to thepercent correct responses p=0.0025, and speech-language age equivalencep=0.0309 for all participants.

A broad range of psychostimulants are contemplated by the presentinvention, and include, but not limited to, by way of example, Adderall®(dextroamphetamine plus amphetamine); atomoxetin (Strattera®); caffeine(Nodoz®, Vivarin®); dextroamphetamine (Dexedrine®); guanfacine(INTUNIV); extended-release tablets: methylphenidate (Concerta°:Metadata®ER: Metadate®CD): pemoline (Cylert®); phentermine (Fastin®,Jonamin®): armodafinil-(NUVIGIL®): benzphetamine (Didrex®):dexmethylphenidate (Foaclin®): diethyipropionate (Tenuate®):lisdexamfetamine dimestylate (Vyvanse®); modafinil (Provigil®);phendimetrizine (Bontril SR®, Prelu-2®); and sibutramine (Meridia®),Quillivant (extended release methylphenidate), Methlyn (immediaterelease methylphenidate). Methylphenidate®; and Dexedrine® arepreferred.

Particularly suitable psychostimulants pursuant to the present inventionfurther include by way of example, methylphenidate anddexmethylphenidiate, as discussed in co-pending applicationPCT/US2012/038312, filed May 17, 2012, and U.S. Ser. No. 14/112,065,filed Oct. 16, 2013 incorporated herein by reference thereto. Extendedrelease, controlled release and immediate release forms methylphenidateare contemplated as useful psychostimulants. Immediate releasemethylphenidate is a preferred psychostimulant.

It is also within the contemplation of the present invention to providea dosage regimen starting with an initial dose of at least about 2.5 mgand increasing the dosage within the same day or in a subsequent day,which increase in dosages would be commensurate with the continuingincrease in speech-language age equivalence, particularly where thedifferential between chronological age and speech-language equivalenceage is substantial prior to treatment.

The foregoing demonstrates that modest dosages of 5.0 to 10 mg/day of apsychostimulant result in an increase in the percentage of correctlypronounced intelligible syllables or words. The percentage increase inthe correctly produced sounds, syllables, words or language is generallyat least about 1.2 fold. The maximum increase is 5 fold in some cases.The foregoing further demonstrates that the increase in correctlypronounced syllables or words persists over time even after thepsychostimulant is no longer efficaciously active or present in thebody.

In the art related to the treatment of hyperactivity in children,particularly including ADD and ADHD, it is established practice toadminister methylphenidate. Psychosocial behavioral disorders such aslack of attentiveness and verbal regression are improved with theadministration of methylphenidate, as disclosed in U.S. Pat. No.6,121,261, issued Sep. 19, 2006 to Glatt et al; and Creager et al.,Journal of Speech and Hearing Research, 623-628 (1967). Methylphenidateis administered daily to children suffering psychobehavioral andneuropsychological disorders. The behavioral improvement is short lived,and lasts, at most, several hours after administration of themethylphenidate. Unless such daily dosages are maintained, the subjectreverts to his or her attention deficits and hyperactivity.

Intensive speech-language therapy sessions over several weeks, asdiscussed hereinbefore in paragraph [0009]. reports an improvement of atbest about 1.14 fold to 1.16 fold in the number of correctly pronouncedsingle or multiple words, whereas in a single psychostimulantadministration pursuant to the present invention, particularly withrespect to Participant 1, there was an about 3.34 fold (See FIG. 2,Session 1).

The foregoing demonstrates persistent improvement of the cerebral palsyimpaired speech and language, and suggests that alternate neuralpathways are being effected. These alternate route neural pathwaysseemingly persist even when the psychostimulant is no longerefficaciously active or present in the body. This seems to indicate thepossibility that alternate pathways have been opened up as a residualeffect of the treatment with the medication.

While the invention has been described and illustrated with reference tocertain particular embodiments thereof, those skilled in the art willappreciate that various adaptations, changes, modifications,substitutions, deletions, or additions of procedures and protocols maybe made without departing from the spirit and scope of the invention.For example, effective dosages other than the particular dosages as setforth herein above may be applicable as a consequence of variations inthe responsiveness of the subject being treated for any of theindications with the compounds of the invention indicated above.Likewise, the specific pharmacological responses observed may varyaccording to and depending upon the particular active compounds selectedor whether there are present pharmaceutical carriers, as well as thetype of formulation and mode of administration employed, and suchexpected variations or differences in the results are contemplated inaccordance with the objects and practices of the present invention. Itis intended, therefore, that the invention be defined by the scope ofthe claims which follow and that such claims be interpreted as broadlyas is reasonable.

What is claimed is:
 1. A method for treating speech impairment secondaryto cerebral palsy in a subject in need of such treatment, said methodcomprises: (a) providing a psychostimulant; (b) administering thepsychostimulant in a therapeutically effective dose to the subject;whereby the speech impairment is improved.
 2. The method of claim 1,wherein the subject has a chronological age greater than thespeech-language age equivalence prior to step (a) and the differencebetween the chronological age and speech language age equivalence isdiminished after step (b).
 3. The method of claim 1, wherein there is adiminished difference in chronological age to speech-language ageequivalence that persists after the psychostimulant is no longerefficaciously active in the subject.
 4. The method of claim 1, whereinthe subject is unable to pronounce one or more of the bilabialconsonants prior to step (a) and is able to pronounce the one or morebilabial consonants after step (b).
 5. The method of claim 1, whereinsteps (a) and (b) are repeated periodically over a period of time andwherein the diminishment in the impaired speech continues over theperiod of time.
 6. The method of claim 1, wherein further comprisingprior to step (a) determining the cognitive functional age of thesubject through non-verbal means, and wherein the cognitive functionalage is at least about two years.
 7. The method of claim 1, wherein theimproved speech impairment comprises a percentage increase in correctlypronounced syllables and words of from at least about 1.2 fold toupwards of 5 fold.
 8. The method of claim 1, wherein the subject is achild or adolescent.
 9. The method of claim 8, wherein the speechimpairment comprises severe dysarthric speech, and the child oradolescent prior to steps (a) and (b), has no or limited bilabialfunctionality, and after step (b) has improved bilabial functionality.10. The method of claim 1 comprises a psychostimulant
 11. The method ofclaim 1, wherein the psychostimulant comprises an amphetamine.
 12. Amethod for evaluating a subject for the psychostimulant treatment of aspeech impairment secondary to cerebral palsy, said method comprises:(a) diagnosing the subject as having cerebral palsy; (b) determining thesubject has a speech impairment secondary to the cerebral palsy; (c)determining the subject has a threshold cognitive capacity; and whereinwhen the subject has cerebral palsy impaired speechand the thresholdcognitive capacity, the subject is a candidate for psychostimulanttreatment to diminish the speech impairment.
 13. The method of claim 12,step (c) further comprises determining the cognitive age of the subject,and wherein the chronological age is greater than the cognitive age. 14.The method of claim 12, wherein the threshold cognitive capacity is atleast about a 2 year old.
 15. The method of claim 12, wherein step (b)further comprises measuring the speech-language age equivalence of thesubject; and wherein when the chronological age of the subject isgreater than the speech-language age equivalence of the subject.
 16. Themethod of claim 12, wherein step (a) further comprises determining thatthe subject has a substantially intact frontal lobe.
 17. The method ofclaim 16, wherein step (a) further comprises determining that thesubject has a damaged portion of the brain, and an undamaged portionextending from the substantially intact frontal lobe to the auditorycortex.
 18. The method of claim 12, wherein step (a) further comprisesconducting a brain scan and determining that the subject has asubstantially intact frontal lobe, a damaged portion, and an undamagedportion extending from the frontal lobe to the auditory cortex.
 19. Themethod of claim 12, wherein step (a) further comprises analyzing a brainscan of the subject.
 20. A pharmaceutical intervention for the treatmentof speech impairment secondary to cerebral palsy in a subject in need ofsuch said intervention, said pharmaceutical intervention comprises atherapeutically effective dose of a psychostimulant.
 21. Thepharmaceutical intervention of claim 20, wherein the dose isadministered periodically and the treatment persists after thepsychostimulant is no longer efficaciously active in the body of thesubject and in the absence of or prior to a subsequent dose.
 22. Thepharmaceutical intervention of claim 20, wherein in the subject is achild or adolescent.
 23. A dosage regimen for treating cerebral palsyimpaired speech in a subject comprising; a therapeutically effectivedose of a psychostimulant that effects a alternate neural pathway in thebrain; and wherein there is at least about a 20% to several hundred perunit increase in the percent of correctly pronounced intelligiblesyllables or words after administration of the psychostimulant and anincrease in the speech-language age equivalence of the subject.
 24. Thedosage regimen of claim 23, wherein the subject is a child oradolescent.
 25. The dosage regimen of claim 24, wherein thepsychostimulant comprises a methylphenidate.
 26. The dosage regimen ofclaim 23, wherein the increase in speech-language persists after thepsychostimulant is no longer efficaciously active in the subject. 27.The dosage regimen of claim 26, wherein the psychostimulant comprises anamphetamine.
 28. A method for evaluating a subject for psychostimulanttreatment of a speech impairment secondary to cerebral palsy, saidmethod comprises: (a) diagnosing the subject as having a speechimpairment secondary to cerebral palsy; and (b) determining thecognitive functional age of the subject, wherein the cognitivefunctional age is at least about 2 years, and wherein when thechronological age of the subject is greater than the cognitivefunctional age of the subject, the subject is determined to be asuitable subject for said treatment.
 29. The method of claim 28, whereinstep (a) comprises analyzing a brain scan.
 30. The method of claim 29,wherein analyzing the brain scan comprises determining (i) a damagedportion, (ii) a substantially intact frontal lobe and (iii) an undamagedportion extending from the substantially intact frontal lobe to theauditory cortex.
 31. The method of claim 28, wherein step (b) comprises:Determining; (i) in the subject that the subject is following two-steprelated commands; and (ii) in a non-verbal subject determining that thesubject is: (A) sequencing limited vocalizations; and (B) sequencing thevocalizations to the rhythm of the body movements.
 32. The method ofclaim 31, wherein the speech impairment secondary to cerebral palsycomprises dysarthric speech.
 33. The method of claim 32, wherein thedysarthric speech comprises non-bilabial speech.
 34. A method fortreating a subject having a speech impairment secondary to cerebralpalsy, said method comprises: a) diagnosing the subject as having aspeech impairment secondary to cerebral palsy; (b) determining thecognitive functional age of the subject, wherein the cognitivefunctional age is at least about 2 years, and wherein when thechronological age of the subject is greater than the cognitivefunctional age, the subject is determined to be a suitable subject forsaid treatment; and (c) administering a therapeutically effective doseof a psychostimulant to the suitable subject; whereby thespeech-language age equivalence of the subject is increased.
 35. Themethod of claim 34, wherein step (a) comprises analyzing a brain scan.36. The method of claim 35, wherein analyzing the brain scan comprisesdetermining (i) a damaged portion, (ii) a substantially intact frontallobe and (iii) an undamaged portion extending from the substantiallyintact frontal lobe to the auditory cortex.
 37. The method of claim 34,wherein the subject is a child or adolescent.
 38. The method of claim34, wherein step (b) comprises: Determining; (i) in the subject that thesubject is following two-step related commands; and (ii) in a verbalsubject, determining that the subject is using basic two-wordcombinations; and (iii) in a non-verbal subject determining that thesubject is: (A) sequencing limited vocalizations; and (B) moving thebody to a rhythm when modeled.